The candidate, Anthony J. Donate Ph.D., is a cardiovascular physiologist in the Department of Integrative Physiology at the University of Colorado at Boulder. Dr. Donato's research focuses on the mechanisms mediating vascular aging in humans and how habitual aerobic exercise can preserve and restore vascular health with aging. The aim of the research project is to establish the efficacy of a 12-week aerobic exercise intervention for restoring vascular endothelial function in middle-aged and older men and women by inducing reductions in oxidative stress and increases in nitric oxide bioavailability. The proposed research will use an "integrative" (system to gene) approach to identify the cellular and molecular mechanisms by which habitual exercise restores endothelial function in this group, including measurements of vascular endothelial expression of proteins influencing oxidative stress, inflammation and nitric oxide production. The expected results should provide clinically important information regarding the integrative physiological mechanisms by which habitual aerobic exercise improves vascular endothelial function in middle-aged and older adults.